Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries.

BACKGROUND Radiotherapy for early breast cancer can decrease breast cancer mortality but increase other mortality, mainly from heart disease and lung cancer. The mean cardiac dose from irradiation of a left-sided breast cancer can be two or three times that for a right-sided breast cancer. The mean ipsilateral (ie, on the same side as the breast cancer) lung dose can also be two or three times the mean contralateral lung dose. Particularly during the 1970s, when typical heart and lung exposures were greater than now, the laterality of an irradiated breast cancer could measurably affect cardiac mortality and mortality from cancer of the right or the left lung decades later. This study aimed to assess the hazards in the general US population from routine cancer-registry and death-certificate data. METHODS We analysed data for 308 861 US women with early breast cancer of known laterality (left-sided or right-sided) who were registered in the US Surveillance Epidemiology and End Results (SEER) cancer registries during 1973-2001 and followed prospectively for cause-specific mortality until Jan 1, 2002. FINDINGS 115 165 (37%) received radiotherapy. Among those who did not, tumour laterality was of little relevance to subsequent mortality. For women diagnosed during 1973-82 and irradiated, the cardiac mortality ratio (left versus right tumour laterality) was 1.20 (95% CI 1.04-1.38) less than 10 years afterwards, 1.42 (1.11-1.82) 10-14 years afterwards, and 1.58 (1.29-1.95) after 15 years or more (trend: 2p=0.03). For women diagnosed during 1983-92 and irradiated, the cardiac mortality ratio was 1.04 (0.91-1.18) less than 10 years afterwards and 1.27 (0.99-1.63) 10 or more years afterwards. For women diagnosed during 1993-2001 and irradiated the cardiac mortality ratio was 0.96 (0.82-1.12), with none yet followed for 10 years. Among women irradiated for breast cancer who subsequently developed an ipsilateral or contralateral lung cancer, the lung cancer mortality ratio (ipsilateral versus contralateral) for women diagnosed during 1973-82 and irradiated was 1.17 (0.62-2.19), 2.00 (1.00-4.00), and 2.71 (1.65-4.48), respectively, less than 10 years, 10-14 years, and 15 or more years afterwards (trend: 2p=0.04). For women irradiated after 1982 there is, as yet, little information on lung cancer risks more than 10 years afterwards. INTERPRETATION US breast cancer radiotherapy regimens of the 1970s and early 1980s appreciably increased mortality from heart disease and lung cancer 10-20 years afterwards with, as yet, little direct evidence on the hazards after more than 20 years. Since the early 1980s, improvements in radiotherapy planning should have reduced such risks, but the long-term hazards in the general populations of various countries still need to be monitored directly.

[1]  M. Spitz,et al.  Effects of smoking and radiotherapy on lung carcinoma in breast carcinoma survivors , 2003, Cancer.

[2]  A. Neugut,et al.  Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma , 2003, Cancer.

[3]  J. Haybittle,et al.  Cardiac doses in post-operative breast irradiation. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[4]  Mike Clarke,et al.  Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials , 2000 .

[5]  T. Fornander,et al.  Pulmonary complications following different radiotherapy techniques for breast cancer, and the association to irradiated lung volume and dose , 2001, Breast Cancer Research and Treatment.

[6]  I. Lax,et al.  Evaluation of irradiated heart volumes in stage I breast cancer patients treated with postoperative adjuvant radiotherapy. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  D A Pierce,et al.  Joint Effects of Radiation and Smoking on Lung Cancer Risk among Atomic Bomb Survivors , 2003, Radiation research.

[8]  G. Hanks,et al.  The 1993-94 patterns of care process survey for breast irradiation after breast-conserving surgery-comparison with the 1992 standard for breast conservation treatment. The Patterns of Care Study, American College of Radiology. , 2000, International journal of radiation oncology, biology, physics.

[9]  N. Wolmark,et al.  The incidence of lung carcinoma after surgery for breast carcinoma with and without postoperative radiotherapy , 2003, Cancer.

[10]  J. Cuzick Radiotherapy for breast cancer. , 2005, Journal of the National Cancer Institute.

[11]  B. Schneider MANUAL of the international statistical classification of diseases, injuries, and causes of death. Addendum 1. Supplementary interpretations and instructions for coding causes of death. , 1953, Bulletin of the World Health Organization. Supplement.

[12]  Mike Clarke,et al.  EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS , 1995 .

[13]  J. Vermorken Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials , 2000, The Lancet.

[14]  M. Martel,et al.  Postmastectomy radiotherapy of the chest wall: dosimetric comparison of common techniques. , 2002, International journal of radiation oncology, biology, physics.

[15]  A. Neugut,et al.  Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers , 1994, Cancer.

[16]  R. Jagsi,et al.  Results of a survey regarding irradiation of internal mammary chain in patients with breast cancer: practice is culture driven rather than evidence based. , 2004, International journal of radiation oncology, biology, physics.

[17]  W. Mackillop,et al.  Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  B. Hankey,et al.  The surveillance, epidemiology, and end results program: a national resource. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[19]  J. Lebesque,et al.  Cardiac and lung complication probabilities after breast cancer irradiation. , 2000, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[20]  C. Land,et al.  Coronary heart disease after radiotherapy for peptic ulcer disease. , 2005, International journal of radiation oncology, biology, physics.

[21]  M Baum,et al.  Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  M. Gillin,et al.  Dose to the cardiac vascular and conduction systems in primary breast irradiation. , 1989, Medical dosimetry : official journal of the American Association of Medical Dosimetrists.

[23]  M. Schipper,et al.  Cardiac chamber and coronary artery doses associated with postmastectomy radiotherapy techniques to the chest wall and regional nodes. , 2004, International journal of radiation oncology, biology, physics.

[24]  B. Fowble,et al.  Results of the 1983 patterns of care process survey for definitive breast irradiation. , 1991, International journal of radiation oncology, biology, physics.

[25]  P. Hall,et al.  Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90 000 Swedish women , 2003, BMJ : British Medical Journal.

[26]  Anthony Howell,et al.  Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. , 1995, The New England journal of medicine.

[27]  J. Bradley,et al.  The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart for intact breast radiation. , 2002, International journal of radiation oncology, biology, physics.

[28]  H. Ulmer,et al.  Radiotherapy of Internal Mammary Lymph Nodes in Breast Cancer Principle Considerations on the Basis of Dosimetric Data , 2002, Strahlentherapie und Onkologie.

[29]  M. Stovall,et al.  Lung cancer risk and radiation dose among women treated for breast cancer. , 1994, Journal of the National Cancer Institute.

[30]  James S Goodwin,et al.  Risk of cardiac death after adjuvant radiotherapy for breast cancer. , 2005, Journal of the National Cancer Institute.